Categories: C-S Bond Formation >
Synthesis of sulfides (thioethers) and derivatives
The combination of trimethyl phosphate (TMP) and Ca(OH)2 enables a mild and efficient heteroatom methylation in DMF, water, or under neat conditions, at 80 °C or at room temperature. A series of O-, N-, and S-nucleophiles, including phenols, sulfonamides, N-heterocycles, such as 9H-carbazole, indole derivatives, and 1,8-naphthalimide, and aryl/alkyl thiols, are suitable substrates.
Y. Tang, B. Yu, Synthesis, 2022, 54, 2373-2390.
An efficient, indium triiodide-catalyzed substitution of the acetoxy group in alkyl, benzyl, allyl, and propargyl acetates with thiosilanes provides access to various thioethers.
Y. Nishimoto, A. Okita, M. Yasuda, A. Baba, Org. Lett., 2012, 14, 1846-1849.
S-Alkyl, S-aryl, and S-vinyl thiosulfate sodium salts (Bunte salts), which can readily be prepared from sodium thiosulfate, react with Grignard reagents to give sulfides in good yields. The reaction is amenable to a broad structural array of Bunte salts and Grignard reagents. Importantly, this route to sulfides avoids the use of malodorous thiol starting materials or byproducts.
J. T. Reeves, K. Camara, Z. S. Han, Y. Xu, H. Lee, C. A. Busacca, C. H. Senanayaka, Org. Lett., 2014, 16, 1196-1199.
In three odorless methods for the thioarylation and thioalkylation of different nitroarenes using alkyl halides (Br, Cl), triphenyltin chloride, and arylboronic acids as the coupling partners, Na2S2O3·5H2O, S8/KF, and S8/NaOH systems are found to be effective sources of sulfur in the presence of copper salts. The methods offer use of green solvents, inexpensive catalysts, and user-friendly starting materials.
A. Rostami, A. Rostami, A. Ghaderi, J. Org. Chem., 2015, 80, 8694-8704.
A mild organophotoredox protocol enables the formation of Csp3-S/Se bonds by reacting redox-active esters with thio/selenosulfonates. The reaction offers an unprecedented broad substrate scope and wide functional group tolerance.
Y. Dong, P. Ji, Y. Zhang, C. Wang, X. Meng, W. Wang, Org. Lett., 2020, 22, 9562-9567.
A Zn(OTf)2-catalyzed coupling of alcohols/phenols with unactivated tertiary alkyl bromides and a Cu(OTf)2-catalyzed thiolation of unactivated tertiary alkyl oxalates with thiols provide sterically hindered tertiary alkyl ethers and thioethers.
Y. Gong, Z. Zhu, Q. Qian, W. Zong, H. Gong, Org. Lett., 2021, 23, 1005-1010.
A visible-light-promoted cross-coupling of 4-alkyl-1,4-dihydropyridines with thio-/selenium sulfonates under transition-metal-free conditions provides sulfides or selenides in high yields and chemoselectivity under mild transition-metal-free reaction conditions. Using air as the atmosphere, the reaction provides sulfoxides.
J. Li, X.-E. Yang, S.-L. Wang, L.-L. Zhang, X.-Z. Zhou, S.-Y. Wang, S.-J. Ji, Org. Lett., 2020, 22, 4908-4913.
A convenient thiol-ene reaction is performed under blue-light irradiation and catalyzed by photoactive Lewis basic molecules such as acridine orange or naphthalene-fused N-acylbenzimidazole. It is believed that the process is initiated by a proton-coupled electron transfer process within the complex between the thiol and the Lewis basic catalyst.
V. V. Levin, A. D. Dilman, J. Org. Chem., 2019, 84, 8337-8343.
A reducing system combined with InBr3 and 1,1,3,3-tetramethyldisiloxane (TMDS) enables a direct thioetherification of various aromatic carboxylic acids and thiols in a one-pot procedure, whereas a system combined with InI3 and TMDS underwent thioetherification of aliphatic carboxylic acids with thiols.
N. Sakai, T. Miyazaki, T. Sakamoto, T. Yatsuda, T. Moriya, R. Ikeda, T. Konakahara, Org. Lett., 2012, 14, 4366-4369.
Low catalyst loading of Bi2O3 enables a nontoxic and inexpensive photocatalytic initiation of a mild and selective anti-Markovnikov hydrothiolation of olefins using visible light.
O. O. Fadeyi, J. J. Mousseau, Y. Feng, C. Allais, P. Nuhant, M. Z. Chen, B. Pierce, R. Robinson, Org. Lett., 2015, 17, 5756-5759.
Synthetically useful high-yielding, radical thiol-ene reactions can be initiated by visible light irradiation in the presence of transition metal polypyridyl photocatalysts in the presence of p-toluidine as a redox mediator that is capable of catalyzing the otherwise inefficient photooxidation of thiols to the key thiyl radical intermediate. Thus, co-catalytic oxidants can be important in the design of synthetic reactions involving visible light photoredox catalysis.
E. L. Tyson, Z. L. Niemeyer, T. P. Yoon, J. Org. Chem., 2014, 79, 1427-1436.
A gold-catalyzed hydrothiolation of unactivated alkenes proceeds effectively to give anti-Markovnikov-selective adducts in good yields and in a regioselective manner.
T. Tamai, K. Fujiwara, S. Higashimae, A. Nomoto, A. Ogawa, Org. Lett., 2016, 18, 2114-2117.
The use of visible-light-absorbing transition metal photocatalysts enables an anti-Markovnikov hydrothiolation of olefins. Quenching of the photoexcited Ru*(bpz)32 catalyst with a variety of thiols generates key thiyl radical intermediates, that form adducts with a wide variety of olefins in excellent yield.
E. L Tyson, M. S. Ament, T. P. Yoon, J. Org. Chem., 2013, 78, 2046-2050.
The anti-Markovnikov addition of thiols to alkenes using CeCl3 as catalyst leads to products in very good yields. The reaction occurred under solvent-free conditions at room temperature.
C. C. Silveira, S. R. Mendes, F. M. Líbero, Synlett, 2010, 790-792.
A highly selective anti-Markovnikov addition of thiols to unactivated alkenes in water at room temperature without any additive is a very simple and efficient method for the synthesis of linear thioethers.
B. C. Ranu, T. Mandal, Synlett, 2007, 925-928.
A nickel-catalyzed C-S reductive cross-coupling of alkyl halides with arylthiosilanes provides alkyl aryl thioethers. This reaction offers exquisite chemoselectivity, excellent tolerance of diverse functional groups, and wide applications for late-stage modification of biologically relevant molecules.
Y.-Z. Yang, Y. Li, G.-F. Lv, D.-L. He, J.-H. Li, Org. Lett., 2022, 24, 5116-5119.
The Rh-catalyzed hydrothiolation of 1,3-dienes affords either allylic or homoallylic sulfides. Regioselectivity is dictated by the choice of counterion associated with the Rh center. Coordinating counterions, such as Cl-, favor neutral Rh complexes in which the diene binds η2 to afford homoallylic sulfides.
X.-H. Yang, R. T. Davison, S.-Z. Nie, F. A. Cruz, T. M. McGinnis, V. M. Dong, J. Am. Chem. Soc., 2019, 141, 3006-3013.
A wide range of ynol ethers can be prepared via displacement at an sp center. The same protocol can be applied to the synthesis of synthetically useful thioynol ethers. This reaction, which generates highly functionalized, heteroatom-substituted alkynes, involves radical intermediates.
V. J. Gray, J. Cuthbertson, J. D. Wilden, J. Org. Chem., 2014, 79, 5869-5874.
A chiral iron(III)-salen complex catalyzes a regioselective, enantioselective conjugate addition of thiols to acyclic α,β,γ,δ-unsaturated dienones at the δ carbon to provide δ-thia-α,β-unsaturated ketones in high yield and enantioselectivity. A model providing an explanation for the regio- and stereoselection is proposed.
S. Shaw, J. D. White, Org. Lett., 2015, 17, 4564-4567.
A new synthetic method for the preparation of potassium organotrifluoroborates through nucleophilic substitution of potassium bromo- and iodomethyltrifluoroborates is described. Potassium halomethyltrifluoroborates have been prepared via in situ reaction of n-BuLi with dibromo- and diiodomethane, respectively, in the presence of trialkyl borates, followed by treatment with KHF2.
G. A. Molander, J. Ham, Org. Lett., 2006, 8, 2031-2034.
A general, straightforward and odourless ring-opening reaction allows the preparation of β-hydroxy sulfides from in situ generated S-alkylisothiouronium salts in urea-choline chloride-based deep eutectic solvent (DES). The reaction of epoxides with thiourea in DES yields the corresponding thiiranes.
N. Azizi, Z. Yadollahy, A. Rahimzadeh-oskooee, Synlett, 2014, 25, 1085-1088.
A highly regioselective chlorothiolation of alkenes with sulfonyl chlorides is compatible with a variety of functional groups and can be scaled up to the gram scale. The employment of readily available reactants and mild reaction conditions makes this process very practical.
J. Wei, S. Liang, L. Jiang, Y. Mumtaz, Y.-b. Yi, J. Org. Chem., 2020, 85, 977-984.
Epoxides can be opened under neutral conditions with alcohols and thiols in the presence of a catalytic amount of erbium(III) triflate, affording the corresponding β-alkoxy alcohols and β-hydroxy sulfides in high yields. In water, epoxide ring opening occurs to produce the corresponding diols in good yields.
R. Dalpozzo, M. Nardi, M. Oliverio, R. Paonessa, A. Procopio, Synthesis, 2009, 3433-3438.
An NH4I-promoted and H2O-controlled intermolecular difunctionalization of alkenes provides bis-methylsulfanes and β-hydroxysulfides via methylthiyl radical addition to the double bond to give a carbon-centered radical, which immediately cyclizes to a thiiranium ion, followed by combination with H2O to afford β-hydroxysulfides. In the absence of water, 1,2-disulfenylation takes place.
R. He, X. Chen, Y. Li, Q. Liu, C. Liao, L. Chen, Y. Huang, J. Org. Chem., 2019, 84, 8750-8758.
A sulfoxide reduction/C-S bond metathesis cascade between sulfoxides and alkyl bromides in an ionic liquid provides high-value sulfides without the use of any catalysts or bases. In this cascade, classical Kornblum oxidation is employed to reduce sulfoxides with alkyl bromides. This protocol features high functional tolerance, mild conditions, promising scalability, and a sustainable solvent.
C. Liu, D. Chen, Y. Fu, F. Wang, J. Luo, S. Huang, Org. Lett., 2020, 22, 5701-5705.
A sulfoxide reduction/C-S bond metathesis cascade between sulfoxides and alkyl bromides in an ionic liquid provides high-value sulfides without the use of any catalysts or bases. In this cascade, classical Kornblum oxidation is employed to reduce sulfoxides with alkyl bromides. This protocol features high functional tolerance, mild conditions, promising scalability, and a sustainable solvent.C. Liu, D. Chen, Y. Fu, F. Wang, J. Luo, S. Huang, Org. Lett., 2020, 22, 5701-5705.
A gold-catalyzed reaction of sulfonium and selenium ylides with aryldiazoacetates provides products of a [2,3]-sigmatropic rearrangement in high yields. A reaction of aryl allyl anilines delivers exclusively C-H functionalized products.
F. He, S. Jana, R. M. Koenigs, J. Org. Chem., 2020, 85, 11882-11891.
A direct difunctionalization protocol of alkenes with nitriles and thiols under metal-free synthesis conditions provides various β-acetamido sulfides with very good yields simply by using inexpensive molecular iodine as a catalyst, DMSO as a mild oxidant, and readily available thiols as thiolating reagents.
H. Cui, X. Liu, W. Wei, D. Yang, C. He, T. Zhang, H. Wang, J. Org. Chem., 2016, 81, 2252-2260.
In a direct and efficient method for the acetamidosulfenylation reaction of alkenes, NaI was used as a catalyst, DMSO as the oxidant, nitriles as both the solvent and nucleophiles and stable, readily available Bunte salts as thiolating reagents. The reactions were carried out under mild conditions to provide β-acetamido sulfides in good yields. Moreover, the reaction can be performed with alcohols as nucleophiles.
R. Zhang, Z. Yan, D. Wang, Y. Wang, S. Lin, Synlett, 2017, 28, 1195-1200.
Aziridines undergo an efficient, mild and regioselective ring opening with various thiols in the presence of 5 mol% bismuth triflate to afford the corresponding β-aminosulfides in excellent yields.
J. S. Yadav, B. V. S. Reddy, G. Baishya, P. V. Reddy, S. J. Harshavardhan, Synthesis, 2004, 1854-1858.
Sterically encumbered chiral pyrrolidine derivatives are highly efficient organocatalysts for the direct enantioselective α sulfenylation of aldehydes using an electrophilic sulfur source.
M. Marigo, T. C. Wabnitz, D. Fielenbach, K. A. Jorgensen, Angew. Chem. Int. Ed., 2005, 44, 794-797.
By rendering the α-position of amides electrophilic through a mild and chemoselective umpolung transformation, a broad range of widely available oxygen, nitrogen, sulfur, and halogen nucleophiles can be used to generate α-functionalized amides.
C. R. Gonçalves, M. Lemmerer, C. J. Teskey, P. Adler, D. Kaiser, B. Maryasin, L. González, N. Maulide, J. Am. Chem. Soc., 2019, 141, 18437-18443.
An efficient copper-catalyzed carbenoid insertion reaction of α-diazo carbonyl compounds into Si-H and S-H bonds provides a broad range of α-silylesters and α-thioesters in high yields using 5 mol% of a simple copper(I) salt as catalyst. In addition, α-diazoketones can be converted to α-silylketones in moderate yields.
H. Keipour, A. Jalba, L. Delage-Laurin, T. Ollevier, J. Org. Chem., 2017, 82, 3000-3010.
A regio and anti-selective copper-catalyzed 1,2-hydroxysulfenylation of alkenes can be carried out by the use of disulfides and acetic acid. Reoxidation of intermediate sulfides by oxygen enables the use of both organosulfide groups of the disulfides.
N. Taniguchi, J. Org. Chem., 2006, 71, 7874-7876.
A transition-metal-free, direct, and efficient acetamidosulphenylation reaction of alkenes using nitriles as the nucleophiles offers a broad substrate scope and high regioselectivity and provides straightforward access to acetamidosulfide derivatives in good yields via a radical process.
Y. Zheng, Y. He, G. Rong, X. Zhang, Y. Wang, K. Dong, X. Xu, J. Mao, Org. Lett., 2015, 17, 5444-5447.
p-Toluenesulfonic acid efficiently catalyzes direct nucleophilic substitutions of the hydroxy groups of propargylic alcohols with a large variety of carbon- and heteroatom-centered nucleophiles. Reactions can be conducted under mild conditions and in air without the need for dried solvents.
R. Sanz, A. Martinez, J. M. Alvarez-Gutierrez, F. Rodriquez, Eur. J. Org. Chem., 2006, 1383-1386.
Under basic conditions, nucleophilic addition to gem-difluorostyrenes generates an anionic intermediate that can undergo facile elimination of fluoride to generate α-fluorovinylthioethers. An acid-based catalyst system facilitates simultaneous nucleophilic addition and protonation of the unstable intermediate to afford the desired α,α-difluoroalkylthioethers in high selectivity and good yields.
J. P. Sorrentino, D. L. Orsi, R. A. Altman, J. Org. Chem., 2021, 86, 2297-2311.